Objective: To identify factors that determine the uptake of in-vitro fertilization (IVF), and to determine the predicting effect of the identified factors on the uptake of IVF among couples attending fertility clinic at a tertiary health institution in Benin City, Nigeria. Methods: This study adopted a cross-sectional descriptive design. A self-structured questionnaire tested was validated and administered to 250 couples who attended fertility clinic. Data were collected from March 2021 to June 2021 and were analyzed using the Statistical Package for Social Science (SPSS) version 21. Data were presented and interpreted using descriptive statistics and inferential statistics such as Chi-square, univariate statistics and multivariate logistic regression analysis. Results: Among 250 couples, 154 (61.6％) were willing to adopt IVF. The multivariate logistic regression analysis showed that catholic religion [odds ratio (OR) 0.21, 95％ confident interval (CI) 0.54-0.73], family income (OR 1.50, 95％ CI 1.10-2.00) and age (OR 1.04, 95％ CI 1.01-1.10) were the major factors that determined the uptake of IVF, with P-value of <0.001, 0.018 and 0.031, respectively. Conclusions: The uptake of IVF could be sustained or improved on, if the government should improve on the cost of living for families, and religious leaders need to be encouraged to pass on the information about IVF to their members to be well guided about the possibilities of IVF.